Of increasing interest in the treatment of cellular proliferative or neoplastic diseases is the use of chemotherapeutic agents, either alone or in combination with other treatments, such as surgical, radio- or immunotherapeutic procedures. Since the majority of chemotherapeutic agents tend to exert their antiproliferative activity on a host's cells in a non-specific manner, the dosage that may be administered during a particular treatment is often limited by the systemic toxicity of the agent, i.e. the host's toxic reaction to the presence of the agent.
In order to avoid dose limiting systemic toxicity, methods of local and regional administration of chemotherapeutic agents may be employed, particularly with cellular proliferative diseases characterized by the presence of solid tumors or neoplasms. In local administration, the chemotherapeutic agent is administered at the site of the neoplasm, i.e. intralesionally, while in regional administration the drug is directed to the target organ or tissue after intraarterial, intravesicular, intraperitoneal or subconjunctival administration. The goal of local and regional administration is to limit the systemic exposure of the host to the agent and yet maintain a relatively high concentration of the agent at the site or in the region of administration, thereby providing the possibility of improved antiproliferative activity with reduced host toxicity. However, despite the promise of local and regional administration, with some chemotherapeutic agents successful results have not yet been realized. Problems which have been encountered with some agents are rapid diffusion from the site of administration and/or insufficient internalization of the agent by the abnormal quiescent and proliferative cells. Insufficient internalization of the agent is problematic where high, and potentially systemically toxic, dosages of agent must be administered to achieve a sufficiently high intracellular concentration of the agent.
Accordingly, there is continued interest in the development of improved methods of local and regional administration. Improved methods would provide for increased efficacy and/or reduced systemic toxicity of the local or regionally administered agent.